Cellular mechanics and gene expression in blood vessels

Lehoux, Stéphanie; Tedgui, Alain

doi:10.1016/s0021-9290(02)00441-4

Cited by 279 publications

(209 citation statements)

References 83 publications

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“…There is growing evidence that flow changes may play an active role in the development of aortopathy such as dilatation, aneurysm, or dissection. For example, WSS is known to alter function and gene expression of the endothelial cells lining the initial vessel wall and has been implicated in aortic wall remodeling in previous studies 35. Recent work by Guzzardi et al has shown that regions of increased WSS, measured by 4D flow MRI in BAV patients before aortic valve repair, corresponded with extracellular matrix dysregulation and elastic fiber degeneration in resected tissue samples from the same patients 8.…”

Section: Discussionmentioning

confidence: 98%

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4‐Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

Ooij

Markl

Collins

et al. 2017

JAHA

125

100

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BackgroundWall shear stress (WSS) is a stimulus for vessel wall remodeling. Differences in ascending aorta (AAo) hemodynamics have been reported between bicuspid aortic valve (BAV) and tricuspid aortic valve patients with aortic dilatation, but the confounding impact of aortic valve stenosis (AS) is unknown.Methods and ResultsFive hundred seventy‐one subjects underwent 4‐dimensional flow magnetic resonance imaging in the thoracic aorta (210 right‐left BAV cusp fusions, 60 right‐noncoronary BAV cusp fusions, 245 tricuspid aortic valve patients with aortic dilatation, and 56 healthy controls). There were 166 of 515 (32%) patients with AS. WSS atlases were created to quantify group‐specific WSS patterns in the AAo as a function of AS severity. In BAV patients without AS, the different cusp fusion phenotypes resulted in distinct differences in eccentric WSS elevation: right‐left BAV patients exhibited increased WSS by 9% to 34% (P<0.001) at the aortic root and along the entire outer curvature of the AAo whereas right‐noncoronary BAV patients showed 30% WSS increase (P<0.001) at the distal portion of the AAo. WSS in tricuspid aortic valve patients with aortic dilatation patients with no AS was significantly reduced by 21% to 33% (P<0.01) in 4 of 6 AAo regions. In all patient groups, mild, moderate, and severe AS resulted in a marked increase in regional WSS (P<0.001). Moderate‐to‐severe AS further increased WSS magnitude and variability in the AAo. Differences between valve phenotypes were no longer apparent.Conclusions AS significantly alters aortic hemodynamics and WSS independent of aortic valve phenotype and over‐rides previously described flow patterns associated with BAV and tricuspid aortic valve with aortic dilatation. Severity of AS must be considered when investigating valve‐mediated aortopathy.

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Section: Discussionmentioning

confidence: 98%

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4‐Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

Ooij

Markl

Collins

et al. 2017

JAHA

125

100

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show abstract

“…Co-localization of G proteins and integrins allows a single signal to activate two transmembrane receptors, indicating the indirect involvement of G proteins in integrin-mediated signaling (Lehoux and Tedgui, 2003). Stimulation of early activation of G proteins by cyclic stretch has been reported in cardiac fibroblasts (Gudi et al, 1998).…”

Section: Cellular Mechanotransductionmentioning

confidence: 99%

Mechanoregulation of gene expression in fibroblasts

Wang

Thampatty

Lin

et al. 2007

Gene

218

182

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Mechanical loads placed on connective tissues alter gene expression in fibroblasts through mechanotransduction mechanisms by which cells convert mechanical signals into cellular biological events, such as gene expression of extracellular matrix components (e.g., collagen). This mechanical regulation of ECM gene expression affords maintenance of connective tissue homeostasis. However, mechanical loads can also interfere with homeostatic cellular gene expression and consequently cause the pathogenesis of connective tissue diseases such as tendinopathy and osteoarthritis. Therefore, the regulation of gene expression by mechanical loads is closely related to connective tissue physiology and pathology. This article reviews the effects of various mechanical loading conditions on gene regulation in fibroblasts and discusses several mechanotransduction mechanisms. Future research directions in mechanoregulation of gene expression are also suggested.

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“…The stresses and strains associated with mechanical loads have been shown to influence organisms at various length scales-from molecularlevel changes such as ion channel activity (1,2) and gene expression (3), to cell differentiation (4) and tissue and organ patterning (5,6). Thus, key aspects of biological function are closely linked to the mechanics of living materials, while dysregulations of cell and tissue mechanics are associated with an array of pathologies, from skin blistering to heart disease and cancer (7,8).…”

Section: Introductionmentioning

confidence: 99%

Worms under Pressure: Bulk Mechanical Properties of C. elegans Are Independent of the Cuticle

Gilpin

Uppaluri

Brangwynne

2015

Biophysical Journal

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The mechanical properties of cells and tissues play a well-known role in physiology and disease. The model organism Caenorhabditis elegans exhibits mechanical properties that are still poorly understood, but are thought to be dominated by its collagen-rich outer cuticle. To our knowledge, we use a novel microfluidic technique to reveal that the worm responds linearly to low applied hydrostatic stress, exhibiting a volumetric compression with a bulk modulus, k ¼ 140 5 20 kPa; applying negative pressures leads to volumetric expansion of the worm, with a similar bulk modulus. Surprisingly, however, we find that a variety of collagen mutants and pharmacological perturbations targeting the cuticle do not impact the bulk modulus. Moreover, the worm exhibits dramatic stiffening at higher stresses-behavior that is also independent of the cuticle. The stress-strain curves for all conditions can be scaled onto a master equation, suggesting that C. elegans exhibits a universal elastic response dominated by the mechanics of pressurized internal organs.

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Cellular mechanics and gene expression in blood vessels

Cited by 279 publications

References 83 publications

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4‐Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4‐Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

Mechanoregulation of gene expression in fibroblasts

Worms under Pressure: Bulk Mechanical Properties of C. elegans Are Independent of the Cuticle

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